Synovial distribution of αd/CD18, a novel leukointegrin. Comparison with other integrins and their ligands

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Abstract

Objective. To define the synovial distribution of the novel leukointegrin αd/CD18, and compare this with other members of the β2-integrin family of adhesion molecules, and their counter-receptors.

Methods. Monoclonal antibodies to the CD3, CD14, CD29, CD68, β2-integrin, and immunoglobulin supergene families were used to immunohistologically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid arthritis (RA) patients.

Results. The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, β1-integrin (CD29), the β2-integrins CD11b/CD18 (αm2, Mac-1), and α/CD18, whereas CD11a/CD18 (αL2, lymphocyte function-associated antigen 1) and CD11c/CD18 (αx2, gp150/95) expression is generally absent. In RA synovitis, expression of β2-integrins in the SLC increases in proportion to the degree of hyperplasia. The ratio of cells in the SLC which express CD11c/CD18 increases substantially, approaching that of CD11b/CD18 and αd/CD18, while there is minimal increase in CD11a/CD18 expression. In the sublining areas of the tissues, aggregates and diffuse infiltrates of CD3/CD11a/ICAM-3+ lymphocytes are interspersed among CD68/CD14/CD11b/αd+ macrophages. A number of aggregates demonstrate intense αd staining of the lymphocytes. The synovial endothelium variably expresses intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule 1 (VCAM-1), with minimal evidence of ICAM-3 expression.

Conclusion. The leukointegrin αd/CD18 is expressed constitutively by synovial macrophages and macrophage-like lining cells. In rheumatoid synovitis, the intense coexpression of this integrin and its known counter-receptor, ICAM-3, in the inflammatory infiltrates, suggests a potential role for this adhesion pathway in cellular interactions occurring the synovium.

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